Ethers of vitamin a



Patented Oct. 26, 1948 ICE 1 ETHERS F VIT A Nicholas A. Milas, Belmont, Mass... assig'nor to Research Corporation, New York, N. Y., a corporation of New York No Drawing. Original application February 8, 1940, Serial No. 317,967. Divided and this, ap-- plication April 1, 194:6, Serial No. 58,899

3 Claims. (01. 260-611) The present invention relates to the alkyl others of vitamin A. Alkyl ethers of vitamin A have been prepared and found to be physiologically active. Theyare novel and are essential intermediates in certain methods for the synthesis of the vitamin. The ethers are prepared, in accordance with the present invention, by reacting the metallic vitaminates with alkyl halides or sulfates whereby the metal of the vitaminate is replaced by the alkyl group of the alkyl halide or sulfate yielding the corresponding alkyl ether of the vitamin.

The metal vitaminates readily are prepared by various methods, several of which are described in my Patent No. 2,296,291. A single method will be described hereinafter by way of illustration. 1

The reaction by which theethers of the vitamins are formed from. the vitaminates is illustrated by the following general reaction equations 1 and 2. j

1. no Me+R' hal- ROR' +11. hal

in which R. represents the hydrocarbon portion of the molecule of vitamin A, Me represents a metal, R represents an alkylgroup and hal stands for a halogen.

2. no Me+R'R" soi-mom- -m 3" am in which R is the hydrocarbon portion of the molecule of vitamin A, Me stands for a metal and R. and R" are the same or different alkyl' sroups.

The invention is illustrated by the following specific examples.

Example 1.The mun other of vitamin A were then removed under reduced pressure and the brownish solid residue extracted several times with pure petroleum other the extracts combined and theether removed. The solid residue was recrystallized a number of times from methyl alcohol and found to have a M. P. of 138-142. With antimony trichloride in pure chloroform this product gave a green-blue color which had an absorption spectrum showing four bands with maxima at 0200 A, 56.00 A. 4900 A and 4350 A units the last band being due to the presence of the trityl group. From the extinction coemcient at 6200 A units. it was found to have a potency of 364,000 International vitamin A units per gram exprcssedss vitamin A.-

Example 2.4m methyl ether of vitamin A To cc. of t-butyl alcohol containing 0.1 g. of metallic potassium was added about 1 g. of vitamin A in 50 cc. of anhydrous ether. mediate change of color from light yellow to deep red occurred indicating the formation of the.

potassium vitaminate. The mixture was cooled to 0 and treated with slightly in excess of the temperature, the solvents were removed under reduced pressure and the residue extracted a number of times with pure petroleum ether.

- Attempts to purify this product were not as successful as in the case of the trityl ether since it failed to crystallize. with antimony trichloride it gave a strong greenish-blue coloration the spectrum of which was not taken.

A preliminary biological assay of both the trityl and the methyl ethers of vitamin A gave positive results although the exact potency hasnot yet been determined.

From the foregoing examples it will be appareat that various alkyl ethers of vitamin A may be prepared by the substitution of the corresponding alkyl groups for the metal of the metal vitaminates. As stated the metal vitaminates may be prepared in a variety of ways.

This application is a division of my applica-- tion, Serial No. 317.967 filed February 8, 1940, which is now Patent No. 2,410,893, dated November12,1946. 1 claim:

1. As a new product the methyl ether of vitamin A.

2. As a new product the trityl other of I vitamin A.

considerable solid separating out. The solvents 3. As a ndwproduct a vitamin A ether of the group consisting of the trityl ether.

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Number Name Date o'rm one Kippins et at, Chemistry and Industry. me.

Anim- M1195 Nov. 12, I! 

